The apparatus and a method of the invention are particularly appropriate for the separation of biological fluids comprising an aqueous component and one or more cellular components. For example, potential uses of the invention include: extracting a plasma component and a cellular component (including platelets, white blood cells, and red blood cells) from a volume of whole blood, the cellular component being subsequently filtered so as to remove platelets and white blood cells from the red blood cells; extracting a plasma component, in which a substantial amount of platelets is suspended, and a red blood cell component from a volume of whole blood, the white blood cells being subsequently removed by filtration from the platelet component and the red blood cell component; extracting a plasma component, a platelet component, and a red blood cell component from a volume of whole blood, the white blood cells being subsequently removed by filtration from the platelet component and the red blood cell component.
An apparatus for processing blood components is known from document WO 03/089027. This apparatus comprises a centrifuge adapted to cooperate with an annular separation bag connected to at least one product bag, e.g. a platelet component bag.
The centrifuge includes a rotor having a turntable for supporting the separation bag, and a central compartment for containing the product bag connected to the separation bag; and a squeezing system for squeezing the separation bag and causing the transfer of a separated component (e.g. platelets suspended in plasma) from the separation bag into the product bag.
With this apparatus, a single discrete volume of blood is processed at once.
An object of the present invention is to design a separation apparatus that can process at once at least two discrete volumes of a composite liquid, in particular discrete volumes that may be not the same, and with the proportions of the various components of the composite liquid that may vary from one discrete volume to another one.
According to the invention, a method for separating at least two discrete volumes of a composite liquid into at least a first component and a second component comprises enclosing in at least two separation cells mounted on a rotor at least two separation bags containing two discrete volumes of a composite liquid respectively; storing in a container included in the rotor at least two first satellite bags connected to the at least two separation bags respectively; rotating the rotor; and transferring a volume of hydraulic liquid into at least two interconnected expandable hydraulic chambers located in the at least two separation cells respectively, whereby the hydraulic liquid gets distributed under centrifugation forces in the at least two interconnected hydraulic chambers so as to substantially balance the rotor.
Other features of the method according to the invention are as follows: transferring a volume of hydraulic liquid into the at least two interconnected hydraulic chambers comprises transferring a predetermined volume of hydraulic liquid; transferring a volume of hydraulic liquid into the at least two interconnected hydraulic chambers comprises pumping hydraulic liquid into the at least two interconnected hydraulic chambers; transferring a volume of hydraulic liquid into the at least two interconnected hydraulic chambers comprises connecting a source of hydraulic liquid to the at least two interconnected hydraulic chambers so that a rotation of the rotor causes hydraulic liquid to be transferred from the source of hydraulic liquid into the at least two interconnected hydraulic chambers; rotating the rotor comprises rotating the rotor at a sedimentation speed at which the at least first and a second components sediment in each of the separation bags.
The method further comprises: transferring a first separated component from the at least two separation bags into the at least two first satellite bags connected thereto respectively; and balancing any unbalance of the rotor caused by the transfer of the first separated component into the at least two first satellite bags. Balancing any unbalance of the rotor caused by the transfer of the first separated component into the at least two first satellite component bags comprises respectively storing the at least two first satellite bags in the container against at least two interconnected flexible pouches containing a volume of a liquid secured to a wall of the container, whereby the at least two first satellite bags press against the at least two pouches under centrifugation forces and distribute the volume of liquid in the at least two pouches so as to balance the rotor. Transferring a first separated component from the at least two separation bags into the at least two first satellite bags connected thereto respectively comprises: squeezing the at least two separation bags within the at least two separation cells so as to cause a transfer of at least one fraction of the first component into the at least two first satellite bags connected thereto; detecting a characteristic of a component at a first determined location in each separation bag; stopping transferring the at least one fraction of the first component from each separation bag into the first satellite bag connected thereto, upon detection of the characteristic of a component at the first determined location. The method further comprises changing a speed of the rotor after detecting a characteristic of a component at the first determined location in the separation bag in which such detection occurs last. The method further comprises changing a speed of the rotor after a predetermined period of time after detecting a characteristic of a component at the first determined location in one of the at least two separation bags.
The method further comprises: transferring a second separated component from the at least two separation bags into at least two second satellite bags connected thereto respectively; and balancing any unbalance of the rotor caused by the transfer of the second separated component into the at least two second satellite bags. Balancing any unbalance of the rotor caused by the transfer of the second separated component into the at least two second satellite component bags comprises respectively storing the at least two second satellite bags in the container against the at least two interconnected flexible pouches containing a volume of a liquid secured to a wall of the container, whereby the at least two second satellite bags press against the at least two pouches under centrifugation forces and distribute the volume of liquid in the at least two pouches so as to balance the rotor. Transferring a second separated component from the at least two separation bags into the at least two second satellite bags connected thereto respectively comprises: squeezing one of the at least two separation bags within one of the at least two separation cells so as to cause a transfer of the second component into the second satellite bag connected thereto; detecting a characteristic of a component at a second determined location in either the squeezed separation bag or a tube connecting the squeezed separation bag to a second satellite bag; stopping squeezing the squeezed separation bag upon detection of the characteristic of a component at the second determined location; and successively repeating the above steps with each separation bag of the at least two separation bags.
The method further comprises stopping rotating the rotor after detecting a characteristic of a component at the second determined location in the separation bag or the tube connected thereto in which such detection occurs last.
The method further comprises stopping rotating the rotor after a predetermined period of time after detecting a characteristic of a component at the second determined location in one of the at least two separation bags or the tube connected thereto.
According to the invention, an apparatus for separating at least two discrete volumes of a composite liquid into at least a first component and a second component comprises a centrifuge comprises: a rotor having a rotation axis, comprising at least two separation cells, each for containing a separation bag containing a volume of composite liquid; and a first balancing means for balancing the rotor when the respective weights of the at least two separation bags in the at least two separation cells are different, comprising: at least two expandable hydraulic chambers within the at least two separation cells respectively, and the at least two hydraulic chambers are fluidly interconnected; a source of hydraulic liquid fluidly connected to the at least two hydraulic chambers; and a liquid transferring means for transferring a volume of hydraulic liquid from the hydraulic liquid source into the at least two interconnected hydraulic chambers so as to substantially balance the rotor when two separation bags respectively contained in the at least two different separation cells have different weights.
Other features of the apparatus according to the invention are as follows: The apparatus according further comprises a control unit programmed for causing the liquid transferring means to transfer a predetermined volume of hydraulic liquid from the hydraulic liquid source into the at least two interconnected hydraulic chambers, and the predetermined volume of hydraulic liquid is selected so as to substantially balance the rotor whatever the weights of two separation bags respectively contained in the at least two different separation cells.
The liquid transferring means comprises a pumping means for pumping a volume of hydraulic fluid into the at least two interconnected hydraulic chambers.
The source of hydraulic liquid is fixed with respect to the rotor and is fluidly connected to the at least two hydraulic chambers through a rotary seal.
The liquid transferring means comprises a motor for driving the rotor in rotation and the source of hydraulic liquid is fixed with respect to the rotor, below the at least two separation cells, and is fluidly connected to the hydraulic chambers through a rotary seal, whereby a rotation of the rotor causes the volume of hydraulic liquid to be transferred from the hydraulic liquid source into the hydraulic chambers.
The first balancing means further comprises a valve fitted on a conduit between the source of hydraulic liquid and the rotary seal, for controlling a transfer into the hydraulic chambers of a predetermined volume of hydraulic liquid for balancing the rotor.
The at least two hydraulic chambers are interconnected by a circular conduit centered on the rotation axis, and the circular conduit is connected to each hydraulic chamber to an area thereof that is closer to a periphery of the rotor than to the rotation axis.
The liquid transferring means comprises a motor for driving the rotor in rotation, and the source of hydraulic liquid comprises a reservoir for hydraulic liquid that is mounted on the rotor and is so designed and fluidly connected to the at least two hydraulic chambers that a rotation of the rotor causes a transfer of hydraulic liquid from the reservoir into the at least two hydraulic chambers.
The reservoir comprises a housing defining an internal volume that is symmetrical with respect to the rotation axis and a circular inner area that is the farthest to the rotation axis, and the at least two hydraulic chambers are in fluid communication with this circular area of the reservoir.
The apparatus further comprises: a storage means included in the rotor for storing at least two satellite bags respectively connected to at least two separation bags contained in the at least two separation cells; and a component transferring means for transferring at least one separated component from each separation bag into a satellite bag connected thereto.
The component transferring means comprises a pumping means for pumping hydraulic liquid from the source of hydraulic liquid into the at least two interconnected hydraulic chambers so as to squeeze the at least two separation bags within the at least two separation cells and to cause a component separated therein to flow into a satellite bag connected to each separation bag.
The source of hydraulic liquid is fixed with respect to the rotor, below the at least two separation cells, and is fluidly connected to the at least two hydraulic chambers through a rotary seal, and the component transferring means comprises: a motor for driving the rotor in rotation; and at least one valve member associated with each separation cell for selectively allowing or blocking a flow of fluid between a separation bag and a satellite bag, whereby a rotation of the rotor causes hydraulic liquid to be transferred from the hydraulic liquid source into the at least two hydraulic chambers and to squeeze the at least two separation bags within the at least two separation cells, which causes a component separated in a separation bag to flow into a satellite bag connected thereto when the valve member for allowing or blocking a flow of fluid between the separation bag and the satellite bag is open.
The source of hydraulic liquid comprises a reservoir for hydraulic liquid that is mounted on the rotor and is fluidly connected to the at least two hydraulic chambers, and the component transferring means comprises: a motor for driving the rotor in rotation; and at least one valve member associated with each separation cell for selectively allowing or blocking a flow of fluid between a separation bag and a satellite bag, whereby a rotation of the rotor causes hydraulic liquid to be transferred from the reservoir into the at least two hydraulic chambers and to squeeze the at least two separation bags within the at least two separation cells, which causes a component separated in a separation bag to flow into a satellite bag connected thereto when the valve member for allowing or blocking a flow of fluid between the separation bag and the satellite bag is open.
The apparatus further comprises a second balancing means for balancing the rotor when the at least two satellite bags stored in the storing means cause an unbalance of the rotor.
The storage means comprises a central container around which the at least two separation cells are symmetrically arranged with respect to the rotation axis; and
The second balancing means comprises at least two interconnected flexible pouches partially filled with a liquid, and the pouches are arranged against a wall of the central container so that the at least one satellite bag connected to each separation bag presses onto a pouch during centrifugation.
The storage means comprises a central container around which the at least two separation cells are symmetrically arranged with respect to the rotation axis; and the second balancing means comprises a cylindrical flexible pouch partially filled with a liquid lining a wall of the central container so that the at least one satellite bag connected to each separation bag presses onto the pouch during centrifugation.
The storage means comprises one container associated with each separation cell, the container being located between the separation cell and the rotation axis; and the second balancing means comprises one flexible pouch partially filled with a liquid arranged against a wall of each container so that a satellite bag stored in the container presses onto a pouch during centrifugation, and a flexible pouch in one container is fluidly interconnected with a pouch in another container.
The apparatus further comprises: a storage means included in the rotor for storing at least two first satellite bags respectively connected to at least two separation bags contained in the at least two separation cells; and at least one valve member associated with each separation cell for selectively allowing or blocking a flow of fluid between a separation bag and a first satellite bag, and the at least one valve member is mounted on the rotor so as to be between the associated separation cell and the storage means, with respect to the rotation axis.
The apparatus further comprises: a storage means included in the rotor for storing at least two first satellite bags respectively connected to at least two separation bags contained in the at least two separation cells; and at least one valve member associated with each separation cell for selectively allowing or blocking a flow of fluid between a separation bag and a first satellite bag, and the at least one valve member is mounted on the rotor so that the storage means is between the at least one valve member and the associated separation cell, with respect to the rotation axis.
The apparatus further comprises at least one sensor associated with each separation cell for generating information related to a characteristic of a component separated in a separation bag within the separation cell.
The at least one sensor is mounted on the rotor so as to detect a characteristic of a component in a separation bag contained in the associated separation cell.
The at least one sensor is mounted on the rotor so as to detect a characteristic of a component in a tube connected to a separation bag contained in the associated separation cell.
Each separation cell comprises a substantially closed cavity having a longitudinal axis intersecting the rotation axis of the rotor and comprises a portion closer to the rotation axis of the rotor that is defined by four walls converging towards the longitudinal axis of the cavity.
The longitudinal axis of the cavity of each separation cell intersects the rotation axis of the rotor at an acute angle.
Each separation cell comprises a cavity having a bottom wall, an upper wall and a lower wall, and the hydraulic chamber is underneath a membrane that is lining at least part of either the upper wall or the lower wall of the cavity.
Each separation cell comprises a cavity having a bottom wall, an upper wall, and a lower wall, and the hydraulic chamber comprising a flexible pouch that rests at least on part the lower wall.
The density of the hydraulic liquid is so selected as to be higher than the density of the component having the highest density.
Each separation cell comprises a cavity having a bottom wall, an upper wall, and lower wall, and the hydraulic chamber is defined by an elastic socket that is secured to the separation cell so as to extend between the upper wall and the lower wall.
The density of the hydraulic liquid is so selected as to be between the density of a first component and the density of a second component.
Each separation cell comprises a securing means for securing an upper edge of a separation bag so that the upper edge is the portion of the separation bag that is the closest to the rotation axis.
The apparatus further comprises: at least one sensor associated with each separation cell for generating information related to a characteristic of a component separated in a separation bag within the separation cell; a memory unit for storing at least one change in rotation speed of the rotor; and a control unit programmed: for receiving from the memory the at least one change in rotation speed, and information generated by the at least one sensor associated with each separation cell; and for causing the at least one change in rotation speed in view of information generated by one of the at least one sensor associated with each of the at least two separation cells.
The control unit is programmed for causing the at least one change of rotation speed in view of information generated by the first of the at least one sensor associated with the at least two separation cells that detects a characteristic of a component separated in a separation bag within a separation cell.
The control unit is programmed for causing the at least one change of rotation speed in view of information generated by the last of the at least one sensor associated with the at least two separation cells that detects a characteristic of a component separated in a separation bag within a separation cell.
The apparatus further comprises at least one valve member associated with each separation cell for selectively allowing or blocking a flow of fluid between a separation bag within the separation cell and a satellite bag connected thereto, and the control unit is further programmed for causing at least once in a separation process the at least one valve member associated with a separation cell to block a flow of fluid between a separation bag within the separation cell and a satellite bag connected thereto following a detection of the characteristic of a separated component by the at least one sensor associated with the same separation cell.
The apparatus further comprises at least one valve member associated with each separation cell for selectively allowing or blocking a flow of fluid between a separation bag within the separation cell and a satellite bag connected thereto, and the control unit is further programmed for causing at least once in a separation process the at least one valve member associated with a separation cell to allow a flow of fluid between a separation bag within the separation cell and a satellite bag connected thereto following a detection of the characteristic of a separated component by the at least one sensor associated with another separation cell.
The apparatus further comprises at least one valve member associated with each separation cell for selectively allowing or blocking a flow of fluid between a separation bag within the separation cell and a satellite bag connected thereto, and the control unit is further programmed for: causing the rotor to rotate at a sedimentation speed for separating a least two components in at least two separation bags contained in the at least two separation cell respectively; causing the least one valve member associated with each separation cell to allow a flow of fluid between each separation bag and the satellite bag connected thereto; causing the component transferring means to transfer at least a portion of a separated component from each of the at least two separation bags into the satellite bag connected thereto; causing the least one valve member associated with each separation cell to block a flow of fluid between the separation bag within the separation cell and the satellite bag connected thereto, when the sensor associated with the separation cell detects the characteristic of a separated component.
The control unit is further programmed for: causing the component transferring means to stop transferring a separated component from the at least two separation bags into the satellite bags connected thereto when one sensor associated with one of the at least two the separation cells detects the characteristic of a separated component; causing the component transferring means to transfer a separated component from the at least two separation bags into the satellite bags connected thereto, after the valve member associated with the separation cell associated with the sensor that has detected the characteristic of a separated component has blocked a flow of fluid between the separation bag and the satellite bag connected thereto.
The at least one sensor comprises a first sensor for detecting a characteristic of a separated component in a separation bag within a separation cell; the least one valve member comprises a first valve member for allowing or blocking a flow of fluid between a separation bag and a first satellite bag connected thereto; the control unit is further programmed for controlling an actuation of the first valve member in view of information from the first sensor.
The at least one sensor comprises a second sensor for detecting a characteristic of a separated component in a tube connecting a separation bag to a second satellite bag; the least one valve member comprises a second valve member for allowing or blocking a flow of fluid between a separation bag and a second satellite bag connected thereto; the control unit is further programmed for controlling an actuation of a second valve member in view of information from the second sensor.
According to the invention, a set of bags for separating at least two discrete volumes of a composite liquid into at least a first component and a second component comprises: a collection and separation bag having a median axis, a top and a bottom, for cooperating with a centrifuge so that the median axis of the collection and separation bag substantially intersects the rotation axis, the bottom is the farthest from the rotation axis and the top is the closest to the rotation axis, and the top of the separation bag comprises two edges converging towards a tip located on the median axis; a collection tube having a first end connected to the collection and separation bag; and at least two satellite bags connected to the top of the collection and separation bag, and at least one satellite bag in which a component is to be transferred during a rotation of the centrifuge, is connected to the tip of the collection and separation bag.
Other features of the set of bags according to the invention are as follows: the set of bags further comprises: a first flexible tube having a first end connected to a first satellite bag; a valve section for engaging a first pinch valve of the centrifuge; a second flexible tube having: a first end connected to a second satellite bag; a valve section for engaging a second pinch valve of the centrifuge; and a three-way connector having: an inlet channel for connection to the collection and separation bag; a first outlet channel connected to a second end of the first tube, and a second outlet channel connected to a second end of the second tube, and the three-way connector is so shaped as to allow a section of either one of the first outlet channel and the first tube and a section of either one of the second outlet channel and the second tube to be the closest to the rotation axis when the first valve section is engaged in the first pinch valve and the second valve section is engaged in the second pinch valve.
The section of either one of the first outlet channel and the first tube and the section of either one of the second outlet channel and the second tube that are the closest to the rotation axis when the first valve section is engaged in the first pinch valve and the second valve section is engaged in the second pinch valve, coincide at a meeting point of the first outlet channel and the second outlet channel.
The first outlet channel and the second outlet channel are substantially aligned and the inlet channel is perpendicular thereto.
The section of either one of the first outlet channel and the first tube that is the closest to the rotation axis when the first valve section is engaged in the first pinch valve and the second valve section is engaged in the second pinch valve comprises a section of the first tube between the three way connector and the first valve section, and the section of either one of the second outlet channel and the second tube that is the closest to the rotation axis when the first valve section is engaged in the first pinch valve and the second valve section is engaged in the second pinch valve comprises a section of the second tube between the three way connector and the second valve section.
An angle between the first outlet channel and the inlet channel is between 90 degrees and 180 degrees, and an angle between the second outlet channel and the inlet channel is between 90 degrees and 180 degrees.
The inlet channel, the first outlet channel, and the second outlet channel join in a central location.
The first outlet channel connects to the inlet channel at a first location and the second outlet channel connects to the inlet channel at a second location, the first location being closer to the rotation axis than the second location when the first valve section is engaged in the first pinch valve and the second valve section is engaged in the second pinch valve.
The bag set further comprises a third tube having a first end connected to the tip of the collection and separation bag and a second end connected to the inlet channel. The third tube comprises a detection section for engaging a cell detector of the centrifuge. The bag set further comprises a breakable stopper connected to the third tube.
The bag set is for the separation of whole blood into a plasma component, a platelet component and a red blood cell component, and the first satellite bag is for collecting the plasma component and the second satellite bag is for collecting the platelet component.
The bag set further comprises: a third satellite bag for collecting red blood cells; a third tube having: a first section having a first end connected to the top of the collection and separation bag; and a second section having a second end connected to the third satellite bag; and a leuko-reduction filter having an inlet connected to a second end of the first section of the third tube and an outlet connected to a first end of the second section of the third tube.
The bag set further comprises a needle connected to a second end of the collection tube.
Other features and advantages of the invention will appear from the following description and accompanying drawings, which are to be considered exemplary only.